Recent studies on enzymes and reader proteins for histone crotonylation support a function of histone crotonylation in transcription. However, the enzyme(s) responsible for histone decrotonylation (HDCR) remains poorly defined. Moreover, it remains to be determined if histone crotonylation is physiologically significant and functionally distinct from or redundant to histone acetylation. Here we present evidence that class I histone deacetylases (HDACs) rather than sirtuin family deacetylases (SIRTs) are the major histone decrotonylases, and that histone crotonylation is as dynamic as histone acetylation in mammalian cells. Notably, we have generated novel HDAC1 and HDAC3 mutants with impaired HDAC but intact HDCR activity. Using these mutants we demonstrate that selective HDCR in mammalian cells correlates with a broad transcriptional repression and diminished promoter association of crotonylation but not acetylation reader proteins. Furthermore, we show that histone crotonylation is enriched in and required for self-renewal of mouse embryonic stem cells.

中文翻译：

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I类组蛋白去乙酰化酶是主要的组蛋白去乙酰化酶：组蛋白巴豆酰化在转录中的关键和广泛功能的证据。

用于组蛋白巴豆酰化的酶和阅读器蛋白质的最新研究支持组蛋白巴豆酰化在转录中的功能。然而，负责组蛋白去巴豆酰化（HDCR）的酶仍然定义不清。此外，还有待确定的是，组蛋白巴豆酰化是否在生理上是显着的，并且在功能上与组蛋白乙酰化相异或冗余。在这里，我们提供的证据是，主要的组蛋白降糖基化酶是I类组蛋白去乙酰化酶（HDACs），而不是瑟土因家族的脱乙酰基酶（SIRTs），并且组蛋白的巴豆酰化作用与哺乳动物细胞中的组蛋白乙酰化作用一样动态。值得注意的是，我们已经产生了具有受损的HDAC但完整的HDCR活性的新型HDAC1和HDAC3突变体。使用这些突变体，我们证明哺乳动物细胞中的选择性HDCR与广泛的转录抑制和巴豆酰化而不是乙酰化阅读器蛋白的启动子缔合相关。此外，我们表明，组蛋白巴豆酰化丰富并且是小鼠胚胎干细胞自我更新所必需的。